A number of proliferative skin disorders such as mycosis fungoides, psoriasis, vitiligo, eczema, etc., and cancers, including cell lymphomas, may be treated by the application of photosensitizing chemicals and ultraviolet light. These procedures are known as photochemotherapy or, in the specific case of psoriasis, as PUVA (psoralens ultra violet A radiation). Chemical classes in which such phototherapeutic behavior have been observed are porphyrins, phthalocyanins, and psoralens. Each one of these classes possesses characteristics which makes it less than ideal in the phototherapeutic function: skin staining, suspected mutagenic/carcinogenic properties, poor absorption rates, and systemic toxicity.
While no single mechanism of photodermal action appears able to explain the behavior of all the known classes of photosensitizing chemicals, there is a widely-accepted mechanism for action of the three-ring heterocyclics known as psoralens or furocoumarins [S. T. Isaacs, C. J. Shen, J. E. Hearst, and H. Rapoport, Biochem., 16, 1058 (1977)]. A psoralen with the essential structural requirements indicated by the referenced mechanism is ##STR2## Psoralens intercalate into DNA in the cell nucleus and subsequently enter into photo-induced cross-linking with the DNA by forming 2+2, cyclobutane-like fusions from double bonds 3--4 and 4'--5' in the psoralens to double bonds in the pyrimidine bases. This molecular action in the nucleus, which requires a pair of unsaturation loci in the psoralen therapeutic, has been claimed to be the origin of the established photopharmacology. It is also the major limitation to the more wide-spread clinical use of these agents since mutagenic/carcinogenic activity is a potential side effect of DNA intercalation and subsequent alkylation or drug-linking.